This proposal is designed to extend studies of axonal sprouting induced by antibodies to Nerve Growth Factor (ANTI-NGF). Data collected in this laboratory demonstrate that the central processes of sensory neurons sprout after surgical denervation. Daily administration of Nerve Growth Factor (NGF) did not enhance the sprouting. Conversely, daily administration of ANTI- NGF increased the sensory axon sprouting by 50% in surgically denervated and uninjured mammals. The objectives of the current projects are to extend this work by examining the spinal white matter and the dorsal horn, one of the synaptic sites of the sensory neurons. During the first year of the grant, the axonal number in Lissauer's tract were determined. Specific aims of the proposed project are 1) to quantify the effects on axonal numbers in the dorsal columns and determine the proportion of sensory and propriospinal fibers and 2) to quantify the effects on synaptic number in the dorsal horn of uninjured mammals given ANTI-NGF. The methods will be ultrastructural quantitation of the myelinated and unmyelinated axons of the spinal white matter and stereological techniques applied at the ultrastructural level for the quantitation of synapses in the dorsal horn. Given the intraspinal sprouting may be related to functional recovery and that manipulating levels of endogenous NGF may enhance intraspinal sprouting, these studies may lead to manipulations that are clinically applicable.